The present invention relates to methods of determining blood volume, and more particularly a method of determining blood volume by the indicator dilution technique.
Blood volume measurement data is usable by physicians in a variety of medical fields, including critical care, cardiology, pediatrics and surgery, to identify and quantify the amount of blood loss the patient has suffered, to determine the percentage of red blood cells or hemoglobin the patient has lost, and to help to determine the need for continuing treatment. An estimated twelve million blood transfusions per year are performed in U.S. hospitals. If rapid and economic blood volume measurement equipment were available in a hospital, it would be feasible to routinely perform a blood volume test on every patient for whom a blood transfusion appeared to be indicated. Blood volume measurement would also provide a valuable diagnostic tool in treating certain types of heart and kidney disease.
The ability to accurately measure the quantity or volume of blood in an individual would be expected to be particularly useful in surgical situations. The standard methods of estimating the amount of blood an individual has are called the hematocrit or hemoglobin. These tests actually measure the thickness of an individual's blood. Blood is composed of cells, primarily red cells for carrying oxygen, white cells for fighting infections, and platelets, small cells used for clotting purposes. The remainder of the blood is called the plasma, which is primarily water in which are suspended the cells with various clotting factors and special blood proteins. When an individual bleeds, the body will attempt to maintain the same total blood volume by the transfer of water from other parts of the body into the circulatory system. This process causes a thinning of the blood called anemia. The thinning process may take hours or many days to occur or may never occur completely. When the blood thinning process has not occurred completely, the hematocrit will over-estimate the amount of blood the individual actually has.
The more rapid the blood loss, the less likely the hematocrit will reflect the true picture of the patient's blood volume. For example, an individual who has just donated a pint of blood (usually over a 10-15 minute period) obviously has one pint less blood at the end of the donation than at the beginning. Yet a hematocrit measurement at the beginning and at the end of the donation may be almost unchanged, therefore giving no indication that the individual has just lost a pint of blood. Surgery is a situation in which individuals lose relatively large quantities of blood in a short time. Despite infusion of saline and other blood diluters, the hematocrit is frequently very misleading at the end of surgery as to the quantity of blood lost. Patients may have lost 25 to 35 percent more blood than estimated from hematocrit measurement and the weighing of blood-soaked sponges. Patients losing more than 2 pints may have circulatory collapse when undergoing anesthesia.
At the present time, human blood volume is generally measured by indirect means. Blood volume is estimated indirectly by tests which essentially measure the ratio of red blood cells to the plasma (the fluid in which the blood cells are suspended) in a blood sample. Blood volume is inferred from measurement of the hematocrit (the percentage of the blood which is made up of red blood cells). This indirect measure of blood volume actually measures the degree of plasma dilution of the blood. When the hematocrit of a patient's blood drops, the patient is said to be anemic. When that hematocrit is very low, the physician assumes that the dilution is the result of a loss in blood volume and that the patient may require a blood transfusion.
The current approach to human blood volume measurement has several serious drawbacks. When an individual bleeds after surgery or trauma, the body's immediate response is to constrict blood vessels to maintain circulation with a lesser liquid volume. It may take hours or days for the body's production of plasma, which replaces the fluid loss, to cause the remaining blood cells to become diluted so that the degree of blood loss will be accurately reflected by the hematocrit. In addition, diseases such as cancer or kidney disease may damage the plasma protein system so that the patient is unable to produce sufficient plasma to dilute the remaining red blood cells. If this occurs, the patient's blood deficiency may be seriously underestimated and inadequate or incorrect treatment given. Conversely, disease such as polycythemia (a condition marked by an abnormally large number of red blood cells in the blood) can increase the number of red blood cells although plasma volume remains the same or decreases. The presence of this type of disease may mask a drop in the patient's blood volume which requires transfusion therapy.
Direct measurement of human blood volume can be much more accurate than the indirect methods which are currently used. Direct measurement is currently accomplished by the indicator dilution technique involving the injection into the blood stream of an indicator or tracer, such as a radioactive isotope or chemical dye, attached to either the plasma protein portion of the plasma or the red cell portion of the blood. The degree of dilution of the tracer is inversely related to the volume of the patient's blood. Direct measurement of a patient's plasma volume is usually accomplished by injection directly into the patient of an isotope (such as I.sup.125 or I.sup.131) or a chemical dye, such as Evan's Blue Dye, attached to a plasma protein of a type normally suspended in the plasma. Through chemical analysis or use of a gamma counter, the degree of dilution of the tracer is then ascertained and mathematically related to the absolute measurement of the patient's blood volume.
While these direct measurement techniques can produce a much more accurate measurement of blood volume, they have been subject to multiple problems. Physically, it is impossible to achieve instantaneous total mixing of the tracer with the patient's blood plasma. As the tracer mixes, the dye or radioactive isotope leaves the circulatory system at a variable rate. In addition, the use of tiny amounts of tracer requires extreme precision in the injection and sampling process, with relatively small errors resulting in greatly magnified errors in the final measurement. These errors can occur without detection and can be caused by common factors such as the anti-coagulants which are necessary to obtain a sample. Also, blood samples obtained from a normal peripheral vein do not give a true reading of the mean body hematocrit. Some physicians are unaware of these potential inaccuracies and may erroneously estimate the amount of blood needed for transfusion. A common problem after surgery is estimating the amount of blood loss and the amount of transfusions required to correct blood loss. Notwithstanding the problems, it has been possible using meticulous techniques involving multiple samples and the measurement and calculation of 28 to 36 variables to accurately measure an individual's blood volume at a given instant.
Before measurement of blood volume is useful for purposes of diagnosis and treatment, however, it is necessary for a physician or diagnostician to know the "normal" range of blood volumes for a given individual. Without knowing what is normal for a specific person, the physician cannot determine the degree to which his blood volume readings, even performed with great accuracy, indicate loss of blood or a disease state. Many studies have been conducted to determine what constitutes a normal blood volume range for a specific individual. These studies have used multiple techniques, the most common have been body weight or surface area blood volume ratios. In 1977, an alternative method was developed which provides an explanation for systematic errors which had been noted in previous studies. Using these methods, the alternative method provides a new theoretical framework for these calculations which eliminate these systematic errors. These calculation methods, however, are time-consuming and difficult to perform. This problem, coupled with the previously described difficulty of performing accurate blood volume measurement by direct means, has restricted use of direct measurement of blood volume to research situations.
The many hours required to perform the meticulous techniques, involving multiple samplings and the measurement and calculation of 28 to 36 variables, insure that the resultant accurate measurement is available far too late to provide guidance for the critical decisions which must typically be made instantly or at least in some semblance of real time in order to be of value to a living patient. For the purpose of the present invention, real time decisions are defined as those which can be made within 20 minutes of the taking of the last sample from the patient.
Accordingly, it is an object of the present invention to provide a method for obtaining by direct measurement techniques a measurement of blood volume in real time.
Another object is to provide such a method which determines a true time-zero blood volume from a multi-point calculation.
A further object is to provide such a method which optionally compares the calculated blood volumes to a normal volume for the patient.
It is also an object of the present invention to provide apparatus for carrying out such a method in real time.